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201. Cancer thyroïdien familial non médullaire: actualités cliniques et génétiques

Author

UCL - (SLuc) Service d'endocrinologie et de nutrition, Valdes-Socin, Hernán, Palmeira, Leonor, Burlacu, Maria-Christina, Daly, Adrian F, Bours, Vincent, Beckers, Albert, UCL - (SLuc) Service d'endocrinologie et de nutrition, Valdes-Socin, Hernán, Palmeira, Leonor, Burlacu, Maria-Christina, Daly, Adrian F, Bours, Vincent, and Beckers, Albert

Abstract

Le syndrome de «Familial Non Medullary Thyroid Carcinoma» (FNMTC) suppose l’existence, au sein d’une même famille, de deux ou plusieurs patients avec un cancer thyroïdien non médullaire isolé (papillaire, folliculaire, anaplasique). Le diagnostic de FNMTC est retenu après exclusion d’une présentation syndromique comme celle liée aux syndromes de Cowden, Gardner, ou Werner et au Complexe de Carney. Une centaine de familles de FNMTC ont été bien caractérisées sur le plan génétique, incluant des formes papillaires avec (Ch19p13.2) ou sans oxyphilie (Ch2q21, 6q22), en association avec un goitre multinodulaire (14q32), ou avec un cancer rénal (Ch1q21). Plusieurs gènes de susceptibilité ont été proposés : SRGAP1, NKX2-1, FOXE1, et HABP2. On estime que les cas familiaux représentent moins de 5 % des cancers thyroïdiens. Bien que minoritaires, ils représentent une occasion exceptionnelle d’approfondir notre compréhension de la tumorigenèse du cancer thyroïdien et d’identifier des gènes candidats pouvant participer à leur physiopathologie. A partir d’une revue de la littérature et de notre expérience sur le suivi de huit familles avec FNMTC, nous discutons des aspects épidémiologiques, cliniques, pathologiques et génétiques permettant d’aboutir à un meilleur diagnostic et à une prise en charge de ce syndrome oncologique., [A Familial Non Medullary Thyroid Carcinoma (FNMTC) : a clinical and genetic update]. The syndrome of Familial Non Medullary Thyroid Carcinoma (FNMTC) includes two or more patients with an isolated non-medullary thyroid cancer (papillary, follicular, anaplastic) within the same family. To diagnose FNMTC, the clinician must exclude a syndromic presentation such as the syndromes of Cowden, Gardner or Werner, and the Carney Complex. Up to now, a hundred families with FNMTC have been genetically studied, including forms with (Ch19p13.2) or without oxyphilia (Ch2q21), in association with a multinodular goiter (Ch14q32), or with a renal cancer (Ch1q21). Several candidate genes of susceptibility have been proposed: SRGAP1, NKX2-1, FOXE1 and HABP2. So far, it is considered that familial cases represent less than 5 % of thyroid cancers. Although rare, these cases represent a unique opportunity to improve our understanding of thyroid cancer. The identification of candidate genes will enrich our knowledge of thyroid cancer pathophysiology. Based on the literature and our experience of the follow-up of eight families with FNMTC, we discuss epidemiological, clinical, pathological and genetic aspects of FNMTC with a view to improve the diagnosis and treatment of this disease.

Published
2016

202. Prognostic relevance of epilepsy at presentation in glioblastoma patients

Author

Berendsen, Sharon, Varkila, Meri, Kroonen, Jérôme, Seute, Tatjana, Snijders, Tom J, Kauw, Frans, Spliet, Wim G M, Willems, Marie, Poulet, Christophe, Broekman, Marike L, Bours, Vincent, Robe, Pierre A, Berendsen, Sharon, Varkila, Meri, Kroonen, Jérôme, Seute, Tatjana, Snijders, Tom J, Kauw, Frans, Spliet, Wim G M, Willems, Marie, Poulet, Christophe, Broekman, Marike L, Bours, Vincent, and Robe, Pierre A

Published
2016

203. Prognostic relevance of epilepsy at presentation in glioblastoma patients

Author

ZL Algemene en Acute Nec Medisch, Brain, ZL Neuro-Oncologie Medisch, Pathologie Pathologen staf, Cancer, Berendsen, Sharon, Varkila, Meri, Kroonen, Jérôme, Seute, Tatjana, Snijders, Tom J, Kauw, Frans, Spliet, Wim G M, Willems, Marie, Poulet, Christophe, Broekman, Marike L, Bours, Vincent, Robe, Pierre A, ZL Algemene en Acute Nec Medisch, Brain, ZL Neuro-Oncologie Medisch, Pathologie Pathologen staf, Cancer, Berendsen, Sharon, Varkila, Meri, Kroonen, Jérôme, Seute, Tatjana, Snijders, Tom J, Kauw, Frans, Spliet, Wim G M, Willems, Marie, Poulet, Christophe, Broekman, Marike L, Bours, Vincent, and Robe, Pierre A

Published
2016

206. Genomic studies of multiple myeloma reveal an association between X chromosome alterations and genomic profile complexity

Author

Sticca, Tiberio, primary, Caberg, Jean-Hubert, additional, Wenric, Stephane, additional, Poulet, Christophe, additional, Herens, Christian, additional, Jamar, Mauricette, additional, Josse, Claire, additional, El Guendi, Sonia, additional, Max, Stéphanie, additional, Beguin, Yves, additional, Gothot, André, additional, Caers, Jo, additional, and Bours, Vincent, additional

Published
2016
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207. CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone

Author

Goffart, Nicolas, primary, Lombard, Arnaud, additional, Lallemand, François, additional, Kroonen, Jérôme, additional, Nassen, Jessica, additional, Di Valentin, Emmanuel, additional, Berendsen, Sharon, additional, Dedobbeleer, Matthias, additional, Willems, Estelle, additional, Robe, Pierre, additional, Bours, Vincent, additional, Martin, Didier, additional, Martinive, Philippe, additional, Maquet, Pierre, additional, and Rogister, Bernard, additional

Published
2016
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212. Congenital gigantism in a girl with anterior pituitary hyperplasia new genes for a new disease

Author

UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - SSS/DDUV - Institut de Duve, UCL - (SLuc) Centre de génétique médicale UCL, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service d'endocrinologie et de nutrition, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Unité d'endocrinologie pédiatrique, Lysy, Philippe, Daly, Adrian, Brunelle, Chloé, Caberg, Jean-Hubert, Sznajer, Yves, Gruson, Damien, Marbaix, Etienne, Bours, Vincent, Maiter, Dominique, Beckers, Albert, Beauloye, Véronique, 43ème Congrès Annuel de la Société Belge de Pédiatrie, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, UCL - SSS/DDUV - Institut de Duve, UCL - (SLuc) Centre de génétique médicale UCL, UCL - (SLuc) Service de biochimie médicale, UCL - (SLuc) Service d'endocrinologie et de nutrition, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Unité d'endocrinologie pédiatrique, Lysy, Philippe, Daly, Adrian, Brunelle, Chloé, Caberg, Jean-Hubert, Sznajer, Yves, Gruson, Damien, Marbaix, Etienne, Bours, Vincent, Maiter, Dominique, Beckers, Albert, Beauloye, Véronique, and 43ème Congrès Annuel de la Société Belge de Pédiatrie

Published
2015

213. Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients.

Author

UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Unité d'endocrinologie pédiatrique, Rostomyan, Liliya, Daly, Adrian F, Petrossians, Patrick, Nachev, Emil, Lila, Anurag R, Lecoq, Anne-Lise, Lecumberri, Beatriz, Trivellin, Giampaolo, Salvatori, Roberto, Moraitis, Andreas G, Holdaway, Ian, Kranenburg-van Klaveren, Dianne J, Chiara Zatelli, Maria, Palacios, Nuria, Nozieres, Cecile, Zacharin, Margaret, Ebeling, Tapani, Ojaniemi, Marja, Rozhinskaya, Liudmila, Verrua, Elisa, Jaffrain-Rea, Marie-Lise, Filipponi, Silvia, Gusakova, Daria, Pronin, Vyacheslav, Bertherat, Jerome, Belaya, Zhanna, Ilovayskaya, Irena, Sahnoun-Fathallah, Mona, Sievers, Caroline, Stalla, Gunter K, Castermans, Emilie, Caberg, Jean-Hubert, Sorkina, Ekaterina, Auriemma, Renata Simona, Mittal, Sachin, Kareva, Maria, Lysy, Philippe, Emy, Philippe, De Menis, Ernesto, Choong, Catherine S, Mantovani, Giovanna, Bours, Vincent, De Herder, Wouter, Brue, Thierry, Barlier, Anne, Neggers, Sebastian J C M M, Zacharieva, Sabina, Chanson, Philippe, Shah, Nalini Samir, Stratakis, Constantine A, Naves, Luciana A, Beckers, Albert, UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Unité d'endocrinologie pédiatrique, Rostomyan, Liliya, Daly, Adrian F, Petrossians, Patrick, Nachev, Emil, Lila, Anurag R, Lecoq, Anne-Lise, Lecumberri, Beatriz, Trivellin, Giampaolo, Salvatori, Roberto, Moraitis, Andreas G, Holdaway, Ian, Kranenburg-van Klaveren, Dianne J, Chiara Zatelli, Maria, Palacios, Nuria, Nozieres, Cecile, Zacharin, Margaret, Ebeling, Tapani, Ojaniemi, Marja, Rozhinskaya, Liudmila, Verrua, Elisa, Jaffrain-Rea, Marie-Lise, Filipponi, Silvia, Gusakova, Daria, Pronin, Vyacheslav, Bertherat, Jerome, Belaya, Zhanna, Ilovayskaya, Irena, Sahnoun-Fathallah, Mona, Sievers, Caroline, Stalla, Gunter K, Castermans, Emilie, Caberg, Jean-Hubert, Sorkina, Ekaterina, Auriemma, Renata Simona, Mittal, Sachin, Kareva, Maria, Lysy, Philippe, Emy, Philippe, De Menis, Ernesto, Choong, Catherine S, Mantovani, Giovanna, Bours, Vincent, De Herder, Wouter, Brue, Thierry, Barlier, Anne, Neggers, Sebastian J C M M, Zacharieva, Sabina, Chanson, Philippe, Shah, Nalini Samir, Stratakis, Constantine A, Naves, Luciana A, and Beckers, Albert

Abstract

Despite being a classical growth disorder, pituitary gigantism has not been studied previously in a standardized way. We performed a retrospective, multicenter, international study to characterize a large series of pituitary gigantism patients. We included 208 patients (163 males; 78.4%) with growth hormone excess and a current/previous abnormal growth velocity for age or final height >2 s.d. above country normal means. The median onset of rapid growth was 13 years and occurred significantly earlier in females than in males; pituitary adenomas were diagnosed earlier in females than males (15.8 vs 21.5 years respectively). Adenomas were ≥10 mm (i.e., macroadenomas) in 84%, of which extrasellar extension occurred in 77% and invasion in 54%. GH/IGF1 control was achieved in 39% during long-term follow-up. Final height was greater in younger onset patients, with larger tumors and higher GH levels. Later disease control was associated with a greater difference from mid-parental height (r=0.23, P=0.02). AIP mutations occurred in 29%; microduplication at Xq26.3 - X-linked acrogigantism (X-LAG) - occurred in two familial isolated pituitary adenoma kindreds and in ten sporadic patients. Tumor size was not different in X-LAG, AIP mutated and genetically negative patient groups. AIP-mutated and X-LAG patients were significantly younger at onset and diagnosis, but disease control was worse in genetically negative cases. Pituitary gigantism patients are characterized by male predominance and large tumors that are difficult to control. Treatment delay increases final height and symptom burden. AIP mutations and X-LAG explain many cases, but no genetic etiology is seen in >50% of cases.

Published
2015

214. X-linked acrogigantism syndrome: clinical profile and therapeutic responses.

Author

UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Unité d'endocrinologie pédiatrique, Beckers, Albert, Lodish, Maya Beth, Trivellin, Giampaolo, Rostomyan, Liliya, Lee, Misu, Faucz, Fabio R., Yuan, Bo, Choong, Catherine S., Caberg, Jean-Hubert, Verrua, Elisa, Naves, Luciana Ansaneli, Cheetham, Tim D., Young, Jacques, Lysy, Philippe, Petrossians, Patrick, Cotterill, Andrew, Shah, Nalini Samir, Metzger, Daniel, Castermans, Emilie, Ambrosio, Maria Rosaria, Villa, Chiara, Strebkova, Natalia, Mazerkina, Nadia, Gaillard, Stéphan, Barra, Gustavo Barcelos, Casulari, Luis Augusto, Neggers, Sebastian J., Salvatori, Roberto, Jaffrain-Rea, Marie-Lise, Zacharin, Margaret, Santamaria, Beatriz Lecumberri, Zacharieva, Sabina, Lim, Ee Mun, Mantovani, Giovanna, Zatelli, Maria Chaira, Collins, Michael T, Bonneville, Jean-François, Quezado, Martha, Chittiboina, Prashant, Oldfield, Edward H., Bours, Vincent, Liu, Pengfei, W de Herder, Wouter, Pellegata, Natalia, Lupski, James R., Daly, Adrian F., Stratakis, Constantine A., UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Unité d'endocrinologie pédiatrique, Beckers, Albert, Lodish, Maya Beth, Trivellin, Giampaolo, Rostomyan, Liliya, Lee, Misu, Faucz, Fabio R., Yuan, Bo, Choong, Catherine S., Caberg, Jean-Hubert, Verrua, Elisa, Naves, Luciana Ansaneli, Cheetham, Tim D., Young, Jacques, Lysy, Philippe, Petrossians, Patrick, Cotterill, Andrew, Shah, Nalini Samir, Metzger, Daniel, Castermans, Emilie, Ambrosio, Maria Rosaria, Villa, Chiara, Strebkova, Natalia, Mazerkina, Nadia, Gaillard, Stéphan, Barra, Gustavo Barcelos, Casulari, Luis Augusto, Neggers, Sebastian J., Salvatori, Roberto, Jaffrain-Rea, Marie-Lise, Zacharin, Margaret, Santamaria, Beatriz Lecumberri, Zacharieva, Sabina, Lim, Ee Mun, Mantovani, Giovanna, Zatelli, Maria Chaira, Collins, Michael T, Bonneville, Jean-François, Quezado, Martha, Chittiboina, Prashant, Oldfield, Edward H., Bours, Vincent, Liu, Pengfei, W de Herder, Wouter, Pellegata, Natalia, Lupski, James R., Daly, Adrian F., and Stratakis, Constantine A.

Abstract

X-linked acrogigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological, and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and microduplication of chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in two families was dominant, with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight standard deviation scores (SDS) of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersecretion of GH/IGF1 and usually prolactin, due to a pituitary macroadenoma or hyperplasia. Primary neurosurgical control was achieved with extensive anterior pituitary resection, but postoperative hypopituitarism was frequent. Control with somatostatin analogs was not readily achieved despite moderate to high levels of expression of somatostatin receptor subtype-2 in tumor tissue. Postoperative use of adjuvant pegvisomant resulted in control of IGF1 in all five cases where it was employed. X-LAG is a new infant-onset gigantism syndrome that has a severe clinical phenotype leading to challenging disease management.

Published
2015

215. Circulating microRNA-based screening tool for breast cancer

Author

Frères, Pierre, primary, Wenric, Stéphane, additional, Boukerroucha, Meriem, additional, Fasquelle, Corinne, additional, Thiry, Jérôme, additional, Bovy, Nicolas, additional, Struman, Ingrid, additional, Geurts, Pierre, additional, Collignon, Joëlle, additional, Schroeder, Hélène, additional, Kridelka, Frédéric, additional, Lifrange, Eric, additional, Jossa, Véronique, additional, Bours, Vincent, additional, Josse, Claire, additional, and Jerusalem, Guy, additional

Published
2015
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216. GHRH excess and blockade in X-LAG syndrome

Author

Daly, Adrian F, primary, Lysy, Philippe A, additional, Desfilles, Céline, additional, Rostomyan, Liliya, additional, Mohamed, Amira, additional, Caberg, Jean-Hubert, additional, Raverot, Veronique, additional, Castermans, Emilie, additional, Marbaix, Etienne, additional, Maiter, Dominique, additional, Brunelle, Chloe, additional, Trivellin, Giampaolo, additional, Stratakis, Constantine A, additional, Bours, Vincent, additional, Raftopoulos, Christian, additional, Beauloye, Veronique, additional, Barlier, Anne, additional, and Beckers, Albert, additional

Published
2015
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217. AIPand MEN1mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center

Author

Daly, Adrian F, Cano, David A, Venegas-Moreno, Eva, Petrossians, Patrick, Dios, Elena, Castermans, Emilie, Flores-Martínez, Alvaro, Bours, Vincent, Beckers, Albert, and Soto-Moreno, Alfonso

Abstract

Pituitary adenomas have a high disease burden due to tumor growth/invasion and disordered hormonal secretion. Germline mutations in genes such as MEN1and AIPare associated with early onset of aggressive pituitary adenomas that can be resistant to medical therapy.We performed a retrospective screening study using published risk criteria to assess the frequency of AIPand MEN1mutations in pituitary adenoma patients in a tertiary referral center.Pituitary adenoma patients with pediatric/adolescent onset, macroadenomas occurring ≤30 years of age, familial isolated pituitary adenoma (FIPA) kindreds and acromegaly or prolactinoma cases that were uncontrolled by medical therapy were studied genetically. We also assessed whether immunohistochemical staining for AIP (AIP-IHC) in somatotropinomas was associated with somatostatin analogs (SSA) response.Fifty-five patients met the study criteria and underwent genetic screening for AIP/MEN1mutations. No mutations were identified and large deletions/duplications were ruled out using MLPA. In a cohort of sporadic somatotropinomas, low AIP-IHC tumors were significantly larger (P= 0.002) and were more frequently sparsely granulated (P= 0.046) than high AIP-IHC tumors. No significant relationship between AIP-IHC and SSA responses was seen.Germline mutations in AIP/MEN1in pituitary adenoma patients are rare and the use of general risk criteria did not identify cases in a large tertiary-referral setting. In acromegaly, low AIP-IHC was related to larger tumor size and more frequent sparsely granulated subtype but no relationship with SSA responsiveness was seen. The genetics of pituitary adenomas remains largely unexplained and AIPscreening criteria could be significantly refined to focus on large, aggressive tumors in young patients.

Published
2019
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218. The role of germline AIP, MEN1, PRKAR1A, CDKN1B and CDKN2C mutations in a large cohort of children and adolescents with pituitary adenomas

Author

Stratakis, Constantine A, Tichomirowa, Maria A., Boikos, Sosipatros, Azevedo, Monalisa F., Lodish, Maya, Martari, Marco, Verma, Somya, Daly, Adrian F., Raygada, Margarita, Keil, Meg F., Papademetriou, Jason, Drori-Herishanu, Limor, Horvath, Anelia, Tsang, Kit Man, Nesterova, Maria, Franklin, Sherry, Vanbellinghen, Jean-Francois, Bours, Vincent, Salvatori, Roberto, and Beckers, Albert

Subjects
Male, endocrine system, endocrine system diseases, Adolescent, Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, Intracellular Signaling Peptides and Proteins, Article, Pedigree, Chromogranins, GTP-Binding Protein alpha Subunits, Gs, Multiple Endocrine Neoplasia Type 1, Cyclin-Dependent Kinase Inhibitor p18, Humans, Female, Pituitary Neoplasms, Child, Pituitary ACTH Hypersecretion, Cyclin-Dependent Kinase Inhibitor p27, Germ-Line Mutation
Abstract

The prevalence of germline mutations in MEN1, AIP, PRKAR1A, CDKN1B and CDKN2CI is unknown among pediatric patients with pituitary adenomas (PA). In this study, we screened children with PA for mutations in these genes; somatic GNAS mutations were also studied in a limited number of growth hormone (GH) or prolactin (PRL)-secreting PA. We studied 74 and 6 patients with either isolated Cushing disease (CD) or GH- or PRL-secreting PA, respectively. We also screened four pediatric patients with CD, and four with GH/PRL-secreting tumors who had some syndromic features. There was one AIP mutation (p.Lys103Arg) among 74 CD patients. Two MEN1 mutations that occurred in patients with recurrent or difficult-to-treat disease were found among patients with CD. There was one MEN1 and three AIP mutations (p.Gln307ProfsX104, p.Pro114fsX, p.Lys241X) among pediatric patients with isolated GH- or PRL-secreting PA and one additional MEN1 mutation in a patient with positive family history. There were no mutations in the PRKAR1A, CDKN1B, CDKN2C or GNAS genes. Thus, germline AIP or MEN1 gene mutations are frequent among pediatric patients with GH- or PRL-secreting PA but are significantly rarer in pediatric CD; PRKAR1A mutations are not present in PA outside of Carney complex.

Published
2010

222. Prognostic relevance of epilepsy at presentation in glioblastoma patients

Author

Berendsen, Sharon, primary, Varkila, Meri, additional, Kroonen, Jérôme, additional, Seute, Tatjana, additional, Snijders, Tom J., additional, Kauw, Frans, additional, Spliet, Wim G.M., additional, Willems, Marie, additional, Poulet, Christophe, additional, Broekman, Marike L., additional, Bours, Vincent, additional, and Robe, Pierre A., additional

Published
2015
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223. Clinical and genetic characterization of pituitary gigantism: an international collaborative study in 208 patients

Author

Rostomyan, Liliya, primary, Daly, Adrian F, additional, Petrossians, Patrick, additional, Nachev, Emil, additional, Lila, Anurag R, additional, Lecoq, Anne-Lise, additional, Lecumberri, Beatriz, additional, Trivellin, Giampaolo, additional, Salvatori, Roberto, additional, Moraitis, Andreas G, additional, Holdaway, Ian, additional, Kranenburg - van Klaveren, Dianne J, additional, Chiara Zatelli, Maria, additional, Palacios, Nuria, additional, Nozieres, Cecile, additional, Zacharin, Margaret, additional, Ebeling, Tapani, additional, Ojaniemi, Marja, additional, Rozhinskaya, Liudmila, additional, Verrua, Elisa, additional, Jaffrain-Rea, Marie-Lise, additional, Filipponi, Silvia, additional, Gusakova, Daria, additional, Pronin, Vyacheslav, additional, Bertherat, Jerome, additional, Belaya, Zhanna, additional, Ilovayskaya, Irena, additional, Sahnoun-Fathallah, Mona, additional, Sievers, Caroline, additional, Stalla, Gunter K, additional, Castermans, Emilie, additional, Caberg, Jean-Hubert, additional, Sorkina, Ekaterina, additional, Auriemma, Renata Simona, additional, Mittal, Sachin, additional, Kareva, Maria, additional, Lysy, Philippe A, additional, Emy, Philippe, additional, De Menis, Ernesto, additional, Choong, Catherine S, additional, Mantovani, Giovanna, additional, Bours, Vincent, additional, De Herder, Wouter, additional, Brue, Thierry, additional, Barlier, Anne, additional, Neggers, Sebastian J C M M, additional, Zacharieva, Sabina, additional, Chanson, Philippe, additional, Shah, Nalini Samir, additional, Stratakis, Constantine A, additional, Naves, Luciana A, additional, and Beckers, Albert, additional

Published
2015
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224. X-linked acrogigantism syndrome: clinical profile and therapeutic responses

Author

Beckers, Albert, primary, Lodish, Maya Beth, additional, Trivellin, Giampaolo, additional, Rostomyan, Liliya, additional, Lee, Misu, additional, Faucz, Fabio R, additional, Yuan, Bo, additional, Choong, Catherine S, additional, Caberg, Jean-Hubert, additional, Verrua, Elisa, additional, Naves, Luciana Ansaneli, additional, Cheetham, Tim D, additional, Young, Jacques, additional, Lysy, Philippe A, additional, Petrossians, Patrick, additional, Cotterill, Andrew, additional, Shah, Nalini Samir, additional, Metzger, Daniel, additional, Castermans, Emilie, additional, Ambrosio, Maria Rosaria, additional, Villa, Chiara, additional, Strebkova, Natalia, additional, Mazerkina, Nadia, additional, Gaillard, Stéphan, additional, Barra, Gustavo Barcelos, additional, Casulari, Luis Augusto, additional, Neggers, Sebastian J, additional, Salvatori, Roberto, additional, Jaffrain-Rea, Marie-Lise, additional, Zacharin, Margaret, additional, Santamaria, Beatriz Lecumberri, additional, Zacharieva, Sabina, additional, Lim, Ee Mun, additional, Mantovani, Giovanna, additional, Zatelli, Maria Chaira, additional, Collins, Michael T, additional, Bonneville, Jean-François, additional, Quezado, Martha, additional, Chittiboina, Prashant, additional, Oldfield, Edward H, additional, Bours, Vincent, additional, Liu, Pengfei, additional, de Herder, Wouter W, additional, Pellegata, Natalia, additional, Lupski, James R, additional, Daly, Adrian F, additional, and Stratakis, Constantine A, additional

Published
2015
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226. Endothelial exosomes contribute to the antitumor response during breast cancer neoadjuvant chemotherapy via microRNA transfer

Author

Bovy, Nicolas, primary, Blomme, Benoît, additional, Frères, Pierre, additional, Dederen, Stella, additional, Nivelles, Olivier, additional, Lion, Michelle, additional, Carnet, Oriane, additional, Martial, Joseph A., additional, Noël, Agnès, additional, Thiry, Marc, additional, Jérusalem, Guy, additional, Josse, Claire, additional, Bours, Vincent, additional, Tabruyn, Sébastien P., additional, and Struman, Ingrid, additional

Published
2015
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227. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation

Author

UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Unité d'endocrinologie pédiatrique, Trivellin, Giampaolo, Daly, Adrian F., Faucz, Fabio R., Yuan, Bo, Rostomyan, Liliya, Larco, Darwin O., Schernthaner-Reiter, Marie Helene, Szarek, Eva, Leal, Letícia F., Caberg, Jean-Hubert, Castermans, Emilie, Villa, Chiara, Dimopoulos, Aggeliki, Chittiboina, Prashant, Xekouki, Paraskevi, Shah, Nalini, Metzger, Daniel, Lysy, Philippe, Ferrante, Emanuele, Strebkova, Natalia, Mazerkina, Nadia, Zatelli, Maria Chiara, Lodish, Maya, Horvath, Anelia, de Alexandre, Rodrigo Bertollo, Manning, Allison D., Levy, Isaac, Keil, Margaret F., Sierra, Maria de la Luz, Palmeira, Leonor, Coppieters, Wouter, Georges, Michel, Naves, Luciana A., Jamar, Mauricette, Bours, Vincent, Wu, T. John, Choong, Catherine S., Bertherat, Jerome, Chanson, Philippe, Kamenický, Peter, Farrell, William E., Barlier, Anne, Quezado, Martha, Bjelobaba, Ivana, Stojilkovic, Stanko S., Wess, Jurgen, Costanzi, Stefano, Liu, Pengfei, Lupski, James R., Beckers, Albert, Stratakis, Constantine A., UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Unité d'endocrinologie pédiatrique, Trivellin, Giampaolo, Daly, Adrian F., Faucz, Fabio R., Yuan, Bo, Rostomyan, Liliya, Larco, Darwin O., Schernthaner-Reiter, Marie Helene, Szarek, Eva, Leal, Letícia F., Caberg, Jean-Hubert, Castermans, Emilie, Villa, Chiara, Dimopoulos, Aggeliki, Chittiboina, Prashant, Xekouki, Paraskevi, Shah, Nalini, Metzger, Daniel, Lysy, Philippe, Ferrante, Emanuele, Strebkova, Natalia, Mazerkina, Nadia, Zatelli, Maria Chiara, Lodish, Maya, Horvath, Anelia, de Alexandre, Rodrigo Bertollo, Manning, Allison D., Levy, Isaac, Keil, Margaret F., Sierra, Maria de la Luz, Palmeira, Leonor, Coppieters, Wouter, Georges, Michel, Naves, Luciana A., Jamar, Mauricette, Bours, Vincent, Wu, T. John, Choong, Catherine S., Bertherat, Jerome, Chanson, Philippe, Kamenický, Peter, Farrell, William E., Barlier, Anne, Quezado, Martha, Bjelobaba, Ivana, Stojilkovic, Stanko S., Wess, Jurgen, Costanzi, Stefano, Liu, Pengfei, Lupski, James R., Beckers, Albert, and Stratakis, Constantine A.

Abstract

BACKGROUND: Increased secretion of growth hormone leads to gigantism in children and acromegaly in adults; the genetic causes of gigantism and acromegaly are poorly understood. METHODS: We performed clinical and genetic studies of samples obtained from 43 patients with gigantism and then sequenced an implicated gene in samples from 248 patients with acromegaly. RESULTS: We observed microduplication on chromosome Xq26.3 in samples from 13 patients with gigantism; of these samples, 4 were obtained from members of two unrelated kindreds, and 9 were from patients with sporadic cases. All the patients had disease onset during early childhood. Of the patients with gigantism who did not carry an Xq26.3 microduplication, none presented before the age of 5 years. Genomic characterization of the Xq26.3 region suggests that the microduplications are generated during chromosome replication and that they contain four protein-coding genes. Only one of these genes, GPR101, which encodes a G-protein-coupled receptor, was overexpressed in patients' pituitary lesions. We identified a recurrent GPR101 mutation (p.E308D) in 11 of 248 patients with acromegaly, with the mutation found mostly in tumors. When the mutation was transfected into rat GH3 cells, it led to increased release of growth hormone and proliferation of growth hormone-producing cells. CONCLUSIONS: We describe a pediatric disorder (which we have termed X-linked acrogigantism [X-LAG]) that is caused by an Xq26.3 genomic duplication and is characterized by early-onset gigantism resulting from an excess of growth hormone. Duplication of GPR101 probably causes X-LAG. We also found a recurrent mutation in GPR101 in some adults with acromegaly. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others.).

Published
2014

233. Connexin 30 expression inhibits growth of human malignant gliomas but protects them against radiation therapy

Author

Artesi, Maria, primary, Kroonen, Jerome, additional, Bredel, Markus, additional, Nguyen-Khac, Minh, additional, Deprez, Manuel, additional, Schoysman, Laurent, additional, Poulet, Christophe, additional, Chakravarti, Arnab, additional, Kim, Hyunsoo, additional, Scholtens, Denise, additional, Seute, Tatjana, additional, Rogister, Bernard, additional, Bours, Vincent, additional, and Robe, Pierre A., additional

Published
2014
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237. Identification of a new VHLexon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease

Author

Lenglet, Marion, Robriquet, Florence, Schwarz, Klaus, Camps, Carme, Couturier, Anne, Hoogewijs, David, Buffet, Alexandre, Knight, Samantha J.L., Gad, Sophie, Couvé, Sophie, Chesnel, Franck, Pacault, Mathilde, Lindenbaum, Pierre, Job, Sylvie, Dumont, Solenne, Besnard, Thomas, Cornec, Marine, Dreau, Helene, Pentony, Melissa, Kvikstad, Erika, Deveaux, Sophie, Burnichon, Nelly, Ferlicot, Sophie, Vilaine, Mathias, Mazzella, Jean-Michaël, Airaud, Fabrice, Garrec, Céline, Heidet, Laurence, Irtan, Sabine, Mantadakis, Elpis, Bouchireb, Karim, Debatin, Klaus-Michael, Redon, Richard, Bezieau, Stéphane, Bressac-de Paillerets, Brigitte, Teh, Bin Tean, Girodon, François, Randi, Maria-Luigia, Putti, Maria Caterina, Bours, Vincent, Van Wijk, Richard, Göthert, Joachim R., Kattamis, Antonis, Janin, Nicolas, Bento, Celeste, Taylor, Jenny C., Arlot-Bonnemains, Yannick, Richard, Stéphane, Gimenez-Roqueplo, Anne-Paule, Cario, Holger, and Gardie, Betty

Abstract

Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau (VHL) gene. Since this discovery, additional VHLmutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. VHLis a major tumor suppressor gene, mutations in which were first described in patients presenting with VHL disease, which is characterized by the development of highly vascularized tumors. Here, we identify a new VHLcryptic exon (termed E1′) deep in intron 1 that is naturally expressed in many tissues. More importantly, we identify mutations in E1′ in 7 families with erythrocytosis (1 homozygous case and 6 compound-heterozygous cases with a mutation in E1′ in addition to a mutation in VHLcoding sequences) and in 1 large family with typical VHL disease but without any alteration in the other VHLexons. In this study, we show that the mutations induced a dysregulation of VHLsplicing with excessive retention of E1′ and were associated with a downregulation of VHL protein expression. In addition, we demonstrate a pathogenic role for synonymous mutations in VHLexon 2 that altered splicing through E2-skipping in 5 families with erythrocytosis or VHL disease. In all the studied cases, the mutations differentially affected splicing, correlating with phenotype severity. This study demonstrates that cryptic exon retention and exon skipping are new VHLalterations and reveals a novel complex splicing regulation of the VHLgene. These findings open new avenues for diagnosis and research regarding the VHL-related hypoxia-signaling pathway.

Published
2018
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238. Evidence of association between interferon regulatory factor 5 gene polymorphisms and asthma

Author

Wang, Chuan, Rose-Zerilli, Matthew J, Koppelman, Gerard H, Sandling, Johanna K, Holloway, John W, Postma, Dirkje S, Holgate, Stephen T, Bours, Vincent, Syvänen, Ann-Christine, Dideberg, Vinciane, Wang, Chuan, Rose-Zerilli, Matthew J, Koppelman, Gerard H, Sandling, Johanna K, Holloway, John W, Postma, Dirkje S, Holgate, Stephen T, Bours, Vincent, Syvänen, Ann-Christine, and Dideberg, Vinciane

Abstract

Asthma is a heterogeneous disorder hallmarked by chronic inflammation in the respiratory system. Exacerbations of asthma are correlated with respiratory infections. Considering the implication of interferon regulatory factor 5 (IRF5) in innate and adaptive immunity, we investigated the preferential transmission patterns of ten IRF5 gene polymorphisms in two asthmatic family cohorts. A common IRF5 haplotype was found to be associated with asthma and the severity of asthmatic symptoms. Stratified analysis of subgroups of asthmatic individuals revealed that the associations were more pronounced in nonatopic asthmatic individuals. In addition, the risk alleles of IRF5 polymorphisms for asthma were almost completely opposite to those for autoimmune disorders. Our study provides the first evidence of association between IRF5 and asthma, and sheds light on the related but potentially distinct roles of IRF5 alleles in the pathogenesis of asthma and autoimmune disorders.

Published
2012
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239. In vivo tumorigenesis was observed after injection of in vitro expanded neural crest stem cells isolated from adult bone marrow

Author

Wislet-Gendebien, Sabine, Poulet, Christophe, Neirinckx, Virginie, Hennuy, Benoit, Swingland, James T, Laudet, Emerence, Sommer, Lukas, Shakhova, Olga, Bours, Vincent, Rogister, Bernard, Wislet-Gendebien, Sabine, Poulet, Christophe, Neirinckx, Virginie, Hennuy, Benoit, Swingland, James T, Laudet, Emerence, Sommer, Lukas, Shakhova, Olga, Bours, Vincent, and Rogister, Bernard

Published
2012

240. High prevalence of AIP gene mutations following focused screening in young patients with sporadic pituitary macroadenomas

Author

UCL - (SLuc) Service d'endocrinologie et de nutrition, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, Tichomirowa, Maria A, Barlier, Anne, Daly, Adrian F, Jaffrain-Rea, Marie-Lise, Ronchi, Cristina, Yaneva, Maria, Urban, Jonathan D, Petrossians, Patrick, Elenkova, Atanaska, Tabarin, Antoine, Desailloud, Rachel, Maiter, Dominique, Schürmeyer, Thomas, Cozzi, Renato, Theodoropoulou, Marily, Sievers, Caroline, Bernabeu, Ignacio, Naves, Luciana A, Chabre, Olivier, Montañana, Carmen Fajardo, Hana, Vaclav, Halaby, Georges, Delemer, Brigitte, Aizpún, José Ignacio Labarta, Sonnet, Emmanuel, Longás, Angel Ferrandez, Hagelstein, Marie-Thérèse, Caron, Philippe, Stalla, Günter K, Bours, Vincent, Zacharieva, Sabina, Spada, Anna, Brue, Thierry, Beckers, Albert, UCL - (SLuc) Service d'endocrinologie et de nutrition, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, Tichomirowa, Maria A, Barlier, Anne, Daly, Adrian F, Jaffrain-Rea, Marie-Lise, Ronchi, Cristina, Yaneva, Maria, Urban, Jonathan D, Petrossians, Patrick, Elenkova, Atanaska, Tabarin, Antoine, Desailloud, Rachel, Maiter, Dominique, Schürmeyer, Thomas, Cozzi, Renato, Theodoropoulou, Marily, Sievers, Caroline, Bernabeu, Ignacio, Naves, Luciana A, Chabre, Olivier, Montañana, Carmen Fajardo, Hana, Vaclav, Halaby, Georges, Delemer, Brigitte, Aizpún, José Ignacio Labarta, Sonnet, Emmanuel, Longás, Angel Ferrandez, Hagelstein, Marie-Thérèse, Caron, Philippe, Stalla, Günter K, Bours, Vincent, Zacharieva, Sabina, Spada, Anna, Brue, Thierry, and Beckers, Albert

Abstract

BACKGROUND: Aryl hydrocarbon receptor interacting protein (AIP) mutations (AIPmut) cause aggressive pituitary adenomas in young patients, usually in the setting of familial isolated pituitary adenomas. The prevalence of AIPmut among sporadic pituitary adenoma patients appears to be low; studies have not addressed prevalence in the most clinically relevant population. Hence, we undertook an international, multicenter, prospective genetic, and clinical analysis at 21 tertiary referral endocrine departments. METHODS: We included 163 sporadic pituitary macroadenoma patients irrespective of clinical phenotype diagnosed at <30 years of age. RESULTS: Overall, 19/163 (11.7%) patients had germline AIPmut; a further nine patients had sequence changes of uncertain significance or polymorphisms. AIPmut were identified in 8/39 (20.5%) pediatric patients. Ten AIPmut were identified in 11/83 (13.3%) sporadic somatotropinoma patients, in 7/61 (11.5%) prolactinoma patients, and in 1/16 non-functioning pituitary adenoma patients. Large genetic deletions were not seen using multiplex ligation-dependent probe amplification. Familial screening was possible in the relatives of seven patients with AIPmut and carriers were found in six of the seven families. In total, pituitary adenomas were diagnosed in 2/21 AIPmut-screened carriers; both had asymptomatic microadenomas. CONCLUSION: Germline AIPmut occur in 11.7% of patients <30 years with sporadic pituitary macroadenomas and in 20.5% of pediatric patients. AIPmut mutation testing in this population should be considered in order to optimize clinical genetic investigation and management.

Published
2011

241. Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas : an international collaborative study.

Author

UCL - (SLuc) Service d'endocrinologie et de nutrition, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, Daly, Adrian F, Tichomirowa, Maria A, Petrossians, Patrick, Heliövaara, Elina, Jaffrain-Rea, Marie-Lise, Barlier, Anne, Naves, Luciana A, Ebeling, Tapani, Karhu, Auli, Raappana, Antti, Cazabat, Laure, De Menis, Ernesto, Montañana, Carmen Fajardo, Raverot, Gerald, Weil, Robert J, Sane, Timo, Maiter, Dominique, Neggers, Sebastian, Yaneva, Maria, Tabarin, Antoine, Verrua, Elisa, Eloranta, Eija, Murat, Arnaud, Vierimaa, Outi, Salmela, Pasi I, Emy, Philippe, Toledo, Rodrigo A, Sabaté, Maria Isabel, Villa, Chiara, Popelier, Marc, Salvatori, Roberto, Jennings, Juliet, Longás, Angel Ferrandez, Labarta Aizpún, José Ignacio, Georgitsi, Marianthi, Paschke, Ralf, Ronchi, Cristina, Valimaki, Matti, Saloranta, Carola, De Herder, Wouter, Cozzi, Renato, Guitelman, Mirtha, Magri, Flavia, Lagonigro, Maria Stefania, Halaby, Georges, Corman, Vinciane, Hagelstein, Marie-Thérèse, Vanbellinghen, Jean-François, Barra, Gustavo Barcelos, Gimenez-Roqueplo, Anne-Paule, Cameron, Fergus J, Borson-Chazot, Françoise, Holdaway, Ian, Toledo, Sergio P A, Stalla, Günter K, Spada, Anna, Zacharieva, Sabina, Bertherat, Jerome, Brue, Thierry, Bours, Vincent, Chanson, Philippe, Aaltonen, Lauri A, Beckers, Albert, UCL - (SLuc) Service d'endocrinologie et de nutrition, UCL - SSS/IREC/EDIN - Pôle d'endocrinologie, diabète et nutrition, Daly, Adrian F, Tichomirowa, Maria A, Petrossians, Patrick, Heliövaara, Elina, Jaffrain-Rea, Marie-Lise, Barlier, Anne, Naves, Luciana A, Ebeling, Tapani, Karhu, Auli, Raappana, Antti, Cazabat, Laure, De Menis, Ernesto, Montañana, Carmen Fajardo, Raverot, Gerald, Weil, Robert J, Sane, Timo, Maiter, Dominique, Neggers, Sebastian, Yaneva, Maria, Tabarin, Antoine, Verrua, Elisa, Eloranta, Eija, Murat, Arnaud, Vierimaa, Outi, Salmela, Pasi I, Emy, Philippe, Toledo, Rodrigo A, Sabaté, Maria Isabel, Villa, Chiara, Popelier, Marc, Salvatori, Roberto, Jennings, Juliet, Longás, Angel Ferrandez, Labarta Aizpún, José Ignacio, Georgitsi, Marianthi, Paschke, Ralf, Ronchi, Cristina, Valimaki, Matti, Saloranta, Carola, De Herder, Wouter, Cozzi, Renato, Guitelman, Mirtha, Magri, Flavia, Lagonigro, Maria Stefania, Halaby, Georges, Corman, Vinciane, Hagelstein, Marie-Thérèse, Vanbellinghen, Jean-François, Barra, Gustavo Barcelos, Gimenez-Roqueplo, Anne-Paule, Cameron, Fergus J, Borson-Chazot, Françoise, Holdaway, Ian, Toledo, Sergio P A, Stalla, Günter K, Spada, Anna, Zacharieva, Sabina, Bertherat, Jerome, Brue, Thierry, Bours, Vincent, Chanson, Philippe, Aaltonen, Lauri A, and Beckers, Albert

Abstract

AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively.

Published
2010

242. Analyse génétique du cancer du mammaire chez le rat: étude de lignées congéniques

Author

Szpirer, Claude, Szpirer, Josiane, Pays, Etienne, Urbain, Jacques, Bours, Vincent, Vanhamme, Luc, Marini, Anna Maria, Piessevaux, Géraldine, Szpirer, Claude, Szpirer, Josiane, Pays, Etienne, Urbain, Jacques, Bours, Vincent, Vanhamme, Luc, Marini, Anna Maria, and Piessevaux, Géraldine

Abstract

Doctorat en Sciences, info:eu-repo/semantics/nonPublished

Published
2008

243. Altered White Matter Architecture in BDNF Met Carriers

Author

Ziegler, Erik, primary, Foret, Ariane, additional, Mascetti, Laura, additional, Muto, Vincenzo, additional, Le Bourdiec-Shaffii, Anahita, additional, Stender, Johan, additional, Balteau, Evelyne, additional, Dideberg, Vinciane, additional, Bours, Vincent, additional, Maquet, Pierre, additional, and Phillips, Christophe, additional

Published
2013
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244. A case of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia with a rare FIP1L1 breakpoint.

Author

Lambert, Frédéric, Heimann, Pierre, Herens, C., Chariot, Alain, Bours, Vincent, Lambert, Frédéric, Heimann, Pierre, Herens, C., Chariot, Alain, and Bours, Vincent

Abstract

The idiopathic hypereosinophilic syndrome (HES) has remained for a long time a diagnosis of exclusion. Differential diagnosis between the HES and the related chronic eosinophilic leukemia (CEL) relied on the identification of signs of clonality that allowed, when present, the reclassification of patients as CEL. Recently, a new acquired mutation was described in approximately 50% of the HES/CEL patients: a cryptic deletion on chromosome band 4q12 generating a FIP1L1-PDGFRA fusion gene. According to the World Health Organization classification, this clonal abnormality has been proposed as a new surrogate marker for chronic eosinophilic leukemia diagnosis. Fluorescence in situ hybridization and reverse transcriptase-polymerase chain reaction protocols were developed for an accurate del(4)(q12q12) and FIP1L1-PDGFRA fusion gene detection. Here, we report a patient with a rare FIP1L1 intron 16 breakpoint located outside of the reported FIP1L1 breakpoint region (ie, from FIP1L1 introns 9 to 13). This case illustrates the risk of false-negative results with diagnostic procedures that do not take into account the occurrence of rare FIP1L1 breakpoints. As targeted therapy with tyrosine kinase inhibitors has dramatically changed the prognosis of FIP1L1-PDGFRA (+) CEL, false-negative results could hamper accurate diagnosis and treatment., Case Reports, Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2007

245. An insertion-deletion polymorphism in the interferon regulatory Factor 5 (IRF5) gene confers risk of inflammatory bowel diseases.

Author

Dideberg, Vinciane, Kristjansdottir, Gudlaug, Milani, Lili, Libioulle, C, Sigurdsson, Snaevar, Louis, Edouard, Wiman, Ann-Christin, Vermeire, Séverine, Rutgeerts, Paul, Belaiche, Jacques, Franchimont, Denis, Van Gossum, André, Bours, Vincent, Syvänen, Ann-Christine, Dideberg, Vinciane, Kristjansdottir, Gudlaug, Milani, Lili, Libioulle, C, Sigurdsson, Snaevar, Louis, Edouard, Wiman, Ann-Christin, Vermeire, Séverine, Rutgeerts, Paul, Belaiche, Jacques, Franchimont, Denis, Van Gossum, André, Bours, Vincent, and Syvänen, Ann-Christine

Abstract

The interferon regulatory factor 5 (IRF5) gene encodes a transcription factor that plays an important role in the innate as well as in the cell-mediated immune responses. The IRF5 gene has been shown to be associated with systemic lupus erythematosus and rheumatoid arthritis. We studied whether the IRF5 gene is also associated with inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC). Twelve polymorphisms in the IRF5 gene were genotyped in a cohort of 1007 IBD patients (748 CD and 254 UC) and 241 controls from Wallonia, Belgium. The same polymorphisms were genotyped in a confirmatory cohort of 311 controls and 687 IBD patients (488 CD and 192 UC) from Leuven, Belgium. A strong signal of association [P = 1.9 x 10(-5), odds ratio (OR) 1.81 (1.37-2.39)] with IBD was observed for a 5 bp indel (CGGGG) polymorphism in the promoter region of the IRF5 gene. The association was detectable also in CD patients (P = 6.8 x 10(-4)) and was particularly strong among the UC patients [P = 5.3 x 10(-8), OR = 2.42 (1.76-3.34)]. The association of the CGGGG indel was confirmed in the second cohort [P = 3.2 x 10(-5), OR = 1.59 (1.28-1.98)]. The insertion of one CGGGG unit is predicted to create an additional binding site for the transcription factor SP1. Using an electrophoretic mobility shift assay, we show allele-specific differences in protein binding to this repetitive DNA-stretch, which suggest a potential function role for the CGGGG indel., Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Published
2007

246. Combined treatment with octreotide LAR and pegvisomant in patients with pituitary gigantism: clinical evaluation and genetic screening.

Author

Mangupli, Ruth, Rostomyan, Liliya, Castermans, Emilie, Caberg, Jean-Hubert, Camperos, Paul, Krivoy, Jaime, Cuauro, Elvia, Bours, Vincent, Daly, Adrian, and Beckers, Albert

Abstract

Introduction: Pituitary gigantism is a rare condition caused by growth hormone secreting hypersecretion, usually by a pituitary tumor. Acromegaly and gigantism cases that have a genetic cause are challenging to treat, due to large tumor size and poor responses to some medical therapies (e.g. AIP mutation affected cases and those with X-linked acrogigantism syndrome). Materials and methods: We performed a retrospective study to identify gigantism cases among 160 somatotropinoma patients treated between 1985 and 2015 at the University Hospital of Caracas, Venezuela. We studied clinical details at diagnosis, hormonal responses to therapy and undertook targeted genetic testing. Among the 160 cases, eight patients (six males; 75 %) were diagnosed with pituitary gigantism and underwent genetic analysis that included array comparative genome hybridization for Xq26.3 duplications. Results: All patients had GH secreting pituitary macroadenomas that were difficult to control with conventional treatment options, such as surgery or primary somatostatin receptor ligand (SRL) therapy. Combined therapy (long-acting SRL and pegvisomant) as primary treatment or after pituitary surgery and radiotherapy permitted the normalization of IGF-1 levels and clinical improvement. Novel AIP mutations were the found in three patients. None of the patients had Xq26.3 microduplications. Conclusions: Treatment of pituitary gigantism is frequently challenging; delayed control increases the harmful effects of GH excess, such as, excessive stature and symptom burden, so early diagnosis and effective treatment are particularly important in these cases. [ABSTRACT FROM AUTHOR]

Published
2016
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247. GHRH excess and blockade in X-LAG syndrome.

Author

Daly, Adrian F., Lysy, Philippe A., Desfilles, Céline, Rostomyan, Liliya, Mohamed, Amira, Caberg, Jean-Hubert, Raverot, Veronique, Castermans, Emilie, Marbaix, Etienne, Maiter, Dominique, Brunelle, Chloe, Trivellin, Giampaolo, Stratakis, Constantine A., Bours, Vincent, Raftopoulos, Christian, Beauloye, Veronique, Barlier, Anne, and Beckers, Albert

Subjects
GIGANTISM (Disease), GROWTH disorders, PITUITARY diseases, SOMATOTROPIN, GROWTH hormone releasing factor, PITUITARY gland, GENETICS
Abstract

X-linked acrogigantism (X-LAG) syndrome is a newly described form of inheritable pituitary gigantism that begins in early childhood and is usually associated with markedly elevated GH and prolactin secretion by mixed pituitary adenomas/hyperplasia. Microduplications on chromosome Xq26.3 including the GPR101 gene cause X-LAG syndrome. In individual cases random GHRH levels have been elevated. We performed a series of hormonal profiles in a young female sporadic X-LAG syndrome patient and subsequently undertook in vitro studies of primary pituitary tumor culture following neurosurgical resection. The patient demonstrated consistently elevated circulating GHRH levels throughout preoperative testing, which was accompanied by marked GH and prolactin hypersecretion; GH demonstrated a paradoxical increase following TRH administration. In vitro, the pituitary cells showed baseline GH and prolactin release that was further stimulated by GHRH administration. Co-incubation with GHRH and the GHRH receptor antagonist, acetyl-(D-Arg²)-GHRH (1-29) amide, blocked the GHRH-induced GH stimulation; the GHRH receptor antagonist alone significantly reduced GH release. Pasireotide, but not octreotide, inhibited GH secretion. A ghrelin receptor agonist and an inverse agonist led to modest, statistically significant increases and decreases in GH secretion, respectively. GHRH hypersecretion can accompany the pituitary abnormalities seen in X-LAG syndrome. These data suggest that the pathology of X-LAG syndrome may include hypothalamic dysregulation of GHRH secretion, which is in keeping with localization of GPR101 in the hypothalamus. Therapeutic blockade of GHRH secretion could represent a way to target the marked hormonal hypersecretion and overgrowth that characterizes X-LAG syndrome. [ABSTRACT FROM AUTHOR]

Published
2016
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248. Cytogenetic Studies of Rwandan Pediatric Patients Presenting with Global Developmental Delay, Intellectual Disability and/or Multiple Congenital Anomalies.

Author

Uwineza, Annette, Hitayezu, Janvier, Jamar, Mauricette, Caberg, Jean-Hubert, Murorunkwere, Seraphine, Janvier, Ndinkabandi, Bours, Vincent, and Mutesa, Leon

Subjects
RWANDANS, PEDIATRIC respiratory diseases, HUMAN abnormalities, COGNITIVE ability, DOWN syndrome, TRISOMY 13 syndrome, PATIENTS, DIAGNOSIS of Down syndrome, CHROMOSOME abnormalities, CHROMOSOMES, CYTOGENETICS, DEVELOPMENTAL disabilities, KARYOTYPES, PEOPLE with intellectual disabilities, ACTIVITIES of daily living, MULTIPLE human abnormalities, DIAGNOSIS
Abstract

Global developmental delay (GDD) is defined as a significant delay in two or more developmental domains: gross or fine motor, speech/language, cognitive, social/personal and activities of daily living. Many of these children will go on to be diagnosed with intellectual disability (ID), which is most commonly defined as having an IQ <75 in addition to impairment in adaptive functioning. Cytogenetic studies have been performed in 664 Rwandan pediatric patients presenting GDD/ID and/or multiple congenital abnormalities (MCA). Karyotype analysis was performed in all patients and revealed 260 chromosomal abnormalities. The most frequent chromosomal abnormality was Down syndrome and then Edward syndrome and Patau syndrome. Other identified chromosomal abnormalities included 47,XX,+del(9)(q11), 46,XY,del(13)(q34) and 46,XX,der(22)t(10;22)(p10;p10)mat. In conclusion, our results highlight the high frequency of cytogenetically detectable abnormalities in this series, with implications for the burden on the healthcare. This study demonstrates the importance of cytogenetic analysis in patients with GDD/ID and MCA. [ABSTRACT FROM AUTHOR]

Published
2016
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